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Sci Adv. 2018 Nov 28;4(11):eaau8621. doi: 10.1126/sciadv.aau8621. eCollection 2018 Nov.

An axon initial segment is required for temporal precision in action potential encoding by neuronal populations.

Lazarov E1,2,3,4, Dannemeyer M3,5, Feulner B2,3,6, Enderlein J3,5, Gutnick MJ1, Wolf F2,3,6,7,8,9, Neef A2,3,6,7,8,9.

Author information

Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel.
Max Planck Institute for Dynamics and Self-Organization, Am Faßberg 17, 37077 Göttingen, Germany.
Bernstein Center for Computational Neuroscience, Georg-August-University Göttingen, Am Faßberg 17, 37077 Göttingen, Germany.
University Medical Center Göttingen, Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, Robert Koch Str. 40, 37075 Göttingen, Germany.
III. Institute of Physics, Georg-August-University Göttingen, Friedrich Hund Pl. 1, 37077 Göttingen, Germany.
Max Planck Institute for Experimental Medicine, Hermann Rein St. 3, 37075 Göttingen, Germany.
Institute for Nonlinear Dynamics, Georg-August-University Göttingen, Friedrich Hund Pl. 1, 37077 Göttingen, Germany.
Center for Biostructural Imaging of Neurodegeneration, Von-Siebold-Straße 3A, 37075 Göttingen, Germany.
Campus Institute for Dynamics of Biological Networks, Hermann Rein St. 3, 37075 Göttingen, Germany.


Central neurons initiate action potentials (APs) in the axon initial segment (AIS), a compartment characterized by a high concentration of voltage-dependent ion channels and specialized cytoskeletal anchoring proteins arranged in a regular nanoscale pattern. Although the AIS was a key evolutionary innovation in neurons, the functional benefits it confers are not clear. Using a mutation of the AIS cytoskeletal protein βIV-spectrin, we here establish an in vitro model of neurons with a perturbed AIS architecture that retains nanoscale order but loses the ability to maintain a high NaV density. Combining experiments and simulations, we show that a high NaV density in the AIS is not required for axonal AP initiation; it is, however, crucial for a high bandwidth of information encoding and AP timing precision. Our results provide the first experimental demonstration of axonal AP initiation without high axonal channel density and suggest that increasing the bandwidth of the neuronal code and, hence, the computational efficiency of network function, was a major benefit of the evolution of the AIS.

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